Towards the development of an epitope-focused vaccine for SARS-CoV-2.

The rapid spread of COVID-19 on all continents and the mortality induced by SARS-CoV-2 virus, the cause of the pandemic coronavirus disease 2019 (COVID-19) has motivated an unprecedented effort for vaccine development. Inactivated viruses as well as vaccines focused on the partial or total sequence of the Spike protein using different novel platforms such us RNA, DNA, proteins, and non-replicating viral vectors have been developed. The high global need for vaccines, now and in the future, and the emergence of new variants of concern still requires development of accessible vaccines that can be adapted according to the most prevalent variants in the respective regions. Here, we describe the immunogenic properties of a group of theoretically predicted RBD peptides to be used as the first step towards the development of an effective, safe and low-cost epitope-focused vaccine. One of the tested peptides named P5, proved to be safe and immunogenic. Subcutaneous administration of the peptide, formulated with alumina, induced high levels of specific IgG antibodies in mice and hamsters, as well as an increase of IFN-γ expression by CD8+ T cells in C57 and BALB/c mice upon in vitro stimulation with P5. Neutralizing titers of anti-P5 antibodies, however, were disappointingly low, a deficiency that we will attempt to resolve by the inclusion of additional immunogenic epitopes to P5. The safety and immunogenicity data reported in this study support the use of this peptide as a starting point for the design of an epitope restricted vaccine.

Iron metal-organic framework supported in a polymeric membrane for solid-phase extraction of anti-inflammatory drugs.

A solid-phase extraction methodology using a MIL-101(Fe)/PVDF membrane was proposed as a useful alternative for the simultaneous determination of naproxen, diclofenac, and ibuprofen, three anti-inflammatory drugs (NSAIDs), in wastewater samples by HPLC-CCD analysis. The MIL-101(Fe) was prepared by a rapid microwave-assisted method and supported in a polymeric PVDF membrane. The prepared material was characterized by X-ray diffraction (XRD), nitrogen adsorption-desorption, scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and Fourier-transform infrared spectroscopy (FT-IR). The factors that affect the extraction of the NSAIDs using the MIL-101(Fe)/PVDF membrane as the sample volume, the solution pH and the elution solvent were studied in detail. The selected conditions were 50 mL of sample solution at pH 3 and 5 mL of methanol: acetone (30:70, v v-1) acidified with formic acid at 2% as elution solvent. The analytical method was linear with determination coefficients (r2 ≥ 0.998) in the calibration ranges from 2 to 100 ng mL-1 for naproxen, 20-200 ng mL-1 for diclofenac, and 100-300 ng mL-1 for ibuprofen. The intra and inter-day precision (repeatability and reproducibility, respectively) of the method (RSD%, n = 5) were lower than 4.8% and 7.1%, respectively. The accuracy reported as recovery percentages ranged from 82 to 118%, and the limits of detection were between 1.8 and 32.3 ng mL-1. Moreover, MIL-101(Fe)/PVDF membrane exhibited improved adsorption efficiency compared to that of its analog MIL-101(Cr)/PVDF and the pristine PVDF membranes, obtaining in an easy and rapid (60 min) way a low-cost and low-toxic adsorbent with excellent stability, reusability, mechanic resistance, and simple operation which shows excellent performance.

Dysregulated expression of hypoxia-inducible factors augments myofibroblasts differentiation in idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is an age-related, progressive and lethal disease, whose pathogenesis is associated with fibroblasts/myofibroblasts foci that produce excessive extracellular matrix accumulation in lung parenchyma. Hypoxia has been described as a determinant factor in its development and progression. However, the role of distinct members of this pathway is not completely described. METHODS: By western blot, quantitative PCR, Immunohistochemistry and Immunocitochemistry were evaluated, the expression HIF alpha subunit isoforms 1, 2 & 3 as well, as their role in myofibroblast differentiation in lung tissue and fibroblast cell lines derived from IPF patients. RESULTS: Hypoxia signaling pathway was found very active in lungs and fibroblasts from IPF patients, as demonstrated by the abundance of alpha subunits 1 and 2, which further correlated with the increased expression of myofibroblast marker αSMA. In contrast, HIF-3α showed reduced expression associated with its promoter hypermethylation. CONCLUSIONS: This study lends further support to the involvement of hypoxia in the pathogenesis of IPF, and poses HIF-3α expression as a potential negative regulator of these phenomena.

Selection of Specific Peptides for Coccidioides spp. Obtained from Antigenic Fractions through SDS-PAGE and Western Blot Methods by the Recognition of Sera from Patients with Coccidioidomycosis.

Antigenic fractions of 100, 50, 37, and 28 kDa obtained through the SDS-PAGE method that were more frequently recognized by anti-Coccidioides antibodies in the sera of coccidioidomycosis patients were selected using western blotting. Subsequently, these bands were sequenced, and the obtained proteins were analysed by BLAST to choose peptides specific for Coccidioides spp. from among the shared aligned sequences of related fungi. A peptide specific for C. immitis was selected from the "GPI anchored serine-threonine rich protein OS C. immitis", while from the "uncharacterized protein of C. immitis", we selected a peptide for C. immitis and C. posadasii. These proteins arose from the 100 kDa antigenic fraction. From the protein "fatty acid amide hydrolase 1 of C. posadasii" that was identified from the 50 kDa antigenic fraction, a peptide was selected that recognized C. immitis and C. posadasii. In addition, the analysis of all the peptides (353) of each of the assembled proteins showed that only 35 had 100% identity with proteins of C. immitis and C. posadasii, one had 100% identity with only C. immitis, and one had 100% identity with only C. posadasii. These peptides can be used as diagnostic reagents, vaccines, and antifungals.

Artroplastia total de cadera posterior a una infección por tuberculosis: caso clínico y revisión de la literatura / Total hip arthroplasty for the treatment of tuberculosis: case report and literature review

La tuberculosis persiste siendo un problema importante a nivel mundial. A pesar de que el compromiso de la cadera es infrecuente, su aparición representa un escenario complejo. Presentamos un paciente masculino que desarrolló una infección de la cadera que fue diagnosticada como tuberculosis de forma tardía. El paciente recibió tratamiento médico por 6 meses y luego se realizó una artroplastia total de cadera en dos tiempos, con éxito. Presentamos el reporte de un caso completo, junto a su seguimiento al aão y una revisión de la literatura sobre el tema.

Tuberculosis remains a significant problem worldwide. Even thought hip involvement is an infrequent manifestation, it́s appearance represents a challenging scenario. We present a male patient who developed a hip infection later discovered to be tuberculosis. The patient received a medical treatment protocol for 6 months and was subsequently treated with a two stage total hip arthroplasty. We present the full case report with it́s 1-year outcome and a literature review.

Automated solid-phase extraction of phenolic acids using layered double hydroxide-alumina-polymer disks.

The application of layered double hydroxide-Al2 O3 -polymer mixed-matrix disks for solid-phase extraction is reported for the first time. Al2 O3 is embedded in a polymer matrix followed by an in situ metal-exchange process to obtain a layered double hydroxide-Al2 O3 -polymer mixed-matrix disk with excellent flow-through properties. The extraction performance of the prepared disks is evaluated as a proof of concept for the automated extraction using sequential injection analysis of organic acids (p-hydroxybenzoic acid, 3,4-dihydroxybenzoic acid, gallic acid) following an anion-exchange mechanism. After the solid-phase extraction, phenolic acids were quantified by reversed-phase high-performance liquid chromatography with diode-array detection using a core-shell silica-C18 stationary phase and isocratic elution (acetonitrile/0.5% acetic acid in pure water, 5:95, v/v). High sensitivity and reproducibility were obtained with limits of detection in the range of 0.12-0.25 µg/L (sample volume, 4 mL), and relative standard deviations between 2.9 and 3.4% (10 µg/L, n = 6). Enrichment factors of 34-39 were obtained. Layered double hydroxide-Al2 O3 -polymer mixed-matrix disks had an average lifetime of 50 extractions. Analyte recoveries ranged from 93 to 96% for grape juice and nonalcoholic beer samples.

In-syringe dispersive µ-SPE of estrogens using magnetic carbon microparticles obtained from zeolitic imidazolate frameworks.

Herein, we propose for the first time the use of magnetic porous carbons (MPCs) derived from zeolitic imidazolate frameworks (ZIFs) for the automated in-syringe magnetic dispersive micro-solid phase extraction (D-µ-SPE) of environmental pollutants prior to their analysis using GC-MS. MPCs with dual porosity are obtained from the direct combustion of the ZIF-67, obtaining robust and magnetic porous carbons on the micrometer scale. As proof of concept, this material has been applied for the automated D-µ-SPE of estrogens (estrone, 17ß-estradiol, and 17α-ethynylestradiol) cataloged as Contaminants of Emergent Concern by the Environmental Protection Agency of the United States (US-EPA). The automation of the system provided a good precision given the low relative standard deviations (RSDs) obtained, ranging from 2.70 to 5.90 % for intra-day precision and from 4.6 to 9.55 % for inter-day precision. Furthermore, the clean-up and preconcentration of the sample is easy and quick, as the in-syringe magnetic D-µ-SPE is carried out in less than 20 min. The high porosity, magnetism, and good stability of the MPCs facilitated the automation of the SPE in dispersive mode enabling the analysis of samples with a complex matrix without backpressure or problems related with the clogging of the instrumentation conduits. The applicability of the method to wastewater samples has been demonstrated given the good recoveries attained ranging from 86 to 115 %. Graphical abstract In-syringe dispersive µ-SPE of estrogens using magnetic carbon microparticles prior GC-MS.

A rapid microwave-assisted synthesis of a sodium-cadmium metal-organic framework having improved performance as a CO2 adsorbent for CCS.

We report on a facile and rapid microwave-assisted method for preparing a sodium-cadmium metal-organic framework (having coordinatively unsaturated sodium ions) that considerably shortens the conventional synthesis time from 5 days to 1 hour. The obtained (Na,Cd)-MOF showed an excellent volumetric CO2 adsorption capacity (5.2 mmol cm(-3) at 298 K and 1 bar) and better CO2 adsorption properties than those shown by the same metal-organic framework when synthesized following a more conventional procedure. Moreover, the newly prepared material was found to display high selectivity for adsorption of carbon dioxide over nitrogen, and good regenerability and stability during repeated CO2 adsorption-desorption cycles, which are the required properties for any adsorbent intended for carbon dioxide capture and sequestration (CSS) from the post-combustion flue gas of fossil fuelled power stations.

Seasonal and pandemic influenza H1N1 viruses induce differential expression of SOCS-1 and RIG-I genes and cytokine/chemokine production in macrophages.

BACKGROUND: Infection with pandemic (pdm) A/H1N1 virus induces high levels of pro-inflammatory mediators in blood and lungs of experimental animals and humans. METHODS: To compare the involvement of seasonal A/PR/8/34 and pdm A/H1N1 virus strains in the regulation of inflammatory responses, we analyzed the changes in the whole-genome expression induced by these strains in macrophages and A549 epithelial cells. We also focused on the functional implications (cytokine production) of the differential induction of suppressors of cytokine signaling (SOCS)-1, SOCS-3, retinoid-inducible gene (RIG)-I and interferon receptor 1 (IFNAR1) genes by these viral strains in early stages of the infection. RESULTS: We identified 130 genes differentially expressed by pdm A/H1N1 and A/PR/8/34 infections in macrophages. mRNA levels of SOCS-1 and RIG-I were up-regulated in macrophages infected with the A/PR/8/34 but not with pdm A/H1N1 virus. mRNA levels of SOCS-3 and IFNAR1 induced by A/PR/8/34 and pdm A/H1N1 strains in macrophages, as well as in A549 cells were similar. We found higher levels of IL-6, TNF-α, IL-10, CCL3, CCL5, CCL4 and CXCL8 (p < 0.05) in supernatants from cultures of macrophages infected with the pdm A/H1N1 virus compared to those infected with the A/PR/8/34 strain, coincident with the lack of SOCS-1 and RIG-I expression. In contrast, levels of INF-α were higher in cultures of macrophages 48h after infection with the A/PR/8/34 strain than with the pdm A/H1N1 virus. CONCLUSIONS: These findings suggest that factors inherent to the pdm A/H1N1 viral strain may increase the production of inflammatory mediators by inhibiting SOCS-1 and modifying the expression of antiviral immunity-related genes, including RIG-I, in human macrophages.

Drenaje percutáneo de colecciones intraabdominales guiados por ecografía en la unidad de emergencia / Percutaneous drainage of intraabdominal abscesses performed by echocardiography in emergency unit

El objetivo de este trabajo es evaluar los resultados y complicaciones del drenaje percutáneo de colecciones abdominales guiado por ecografía, realizado por cirujanos en una unidad de emergencia. Se diseño un protocolo prospectivo a ser aplicado a todos los pacientes con sospecha de colecciones intraabdominales que fueran evaluados en la Unidad de Emergencia del Hospital del Salvador o que habiéndose diagnosticado en otra unidad fueran derivados para evaluación a la Unidad de Emergencia. En los pacientes con colecciones se buscó la mejor ventana, se infiltró la zona con anestesia local, bajo visión ecográfica se puncionó con una aguja graduada 18G y luego se introdujo un drenaje 12 F con conductor. Entre enero de 1999 y junio de 2001 se evaluó 52 pacientes con colecciones intraabdominales. En resumen la efectividad del drenaje percutáneo de colecciones intraabdominales fue de 92 por ciento con un 4 por ciento de procedimientos frustos, un 4 por ciento de complicaciones, un 6 por ciento que requirió un segundo drenaje y una mortalidad de 4 por ciento. Nuestros resultados demuestran que el drenaje percutáneo de colecciones intraabdominales realizados por cirujanos es un método seguro y eficiente, con un bajo índice de complicaciones y un éxito superior al 90 por ciento al ser utilizado como único tratamaiento asociado a antibióticos

Cirugía abdominal de urgencia en el adulto mayor / Emergency abdominal surgery in elder adult

En este estudio se revisó de manera retrospectiva los resultados de la cirugía abdominal de urgencia en pacientes mayores de 65 años entre el 1 de enero y el 31 de diciembre del 2000. La población total de estudio fue 205 pacientes, de los cuales 128 fueron mujeres y 77 hombres. Los pacientes se dividieron en dos grupos: grupo A entre 65 y 79 años y grupo B mayores de 79 años, para cada uno se estudió presencia de complicaciones y mortalidad. Se analizó estadísticamente con prueba de Chi cuadrado tomando como significativo un p < 0,05. Las intervenciones quirúrgicas más encontradas correspondieron a patología de pared abdominal 28,8 por ciento, biliar 25,9 por ciento, cavidad peritoneal 18,3 por ciento, coloproctológicas 10,2 por ciento, apendicular 9,8 por ciento. El 21,5 por ciento de los pacientes presentó complicaciones, siendo las más frecuentes las de pared abdominal, broncopulmonar y cardiovasculares. Para el grupo A las complicaciones se presentaron en un 18,3 por ciento y para el grupo B 30,8 por ciento, diferencia estadísticamente no significativa. El 9,8 por ciento de los pacientes estudiados falleció durante la cirugía o en el postoperatorio. Al comparar los grupos estudiados se encontró una mortalidad de 6,5 por ciento para el grupo A y 17,6 por ciento para el grupo B, diferencia estadísticamente significativa. La mortalidad aumenta en relación con la edad, no así las complicaciones que no tiene diferencia estadísticamente significativas entre ambos grupos de edad